NAME OF THE MEDICINE DESCRIPTION PHARMACOLOGY. PRODUCT INFORMATION ALPHAMOX Amoxicillin (as trihydrate)

Transcription

1 PRODUCT INFORMATION ALPHAMOX Amoxicillin (as trihydrate) NAME OF THE MEDICINE Active ingredient : Amoxicillin (as trihydrate) Chemical name : (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7- oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Structural formula : Molecular formula : C 16H 19N 3O 5S, 3H 2O Molecular weight : CAS Registry no. : DESCRIPTION Amoxicillin trihydrate is a white or almost white, crystalline powder, which is slightly soluble in water and in ethanol (96%) and is practically insoluble in chloroform, in ether, and in fixed oils. Each ALPHAMOX 250 and ALPHAMOX 500 capsule contains amoxicillin trihydrate equivalent to 250 mg and 500 mg amoxicillin, respectively. The capsules also contain the following inactive ingredients: purified talc, magnesium stearate, sodium starch glycollate, colloidal anhydrous silica, sodium lauryl sulfate, gelatin, titanium dioxide, brilliant blue FCF CI42090, iron oxide yellow CI77492, microcrystalline cellulose [ALPHAMOX 250 only]. Each bottle of ALPHAMOX 125 suspension contains 125 mg per 5 ml of amoxicillin when reconstituted. Each bottle of ALPHAMOX 250 suspension contains 250 mg per 5 ml of amoxicillin when reconstituted. The suspensions also contain the following inactive ingredients: sodium benzoate, propylene glycol alginate, colloidal anhydrous silica, aspartame, disodium edetate, sodium citrate dihydrate, sorbitol, Raspberry Flavour Permaseal PHARMACOLOGY Microbiology Amoxicillin is similar to ampicillin in its bactericidal action against Gram-positive and Gram-negative susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of the cell wall mucopeptide. Amoxicillin is active in vitro against most strains of Haemophilus influenzae*, Neisseria gonorrhoeae *, Neisseria meningitidis, Escherichia coli *, Proteus mirabilis * and Salmonellae. Because amoxicillin does not resist destruction by penicillinase, it is not active against penicillinase-producing organisms, particularly penicillinase-producing staphylococci. * Activity refers only to betalactamase negative strains.

2 ALPHAMOX PRODUCT INFORMATION 2 All strains of Pseudomonas species, Klebsiella species, Enterobacter species, indole-positive Proteus species, Serratia marcescens, Citrobacter species, penicillinase producing N. gonorrhoeae and penicillinase producing H. influenzae are resistant. In vitro studies have demonstrated the susceptibility of most strains of the following gram-positive bacteria: alpha- and beta-haemolytic streptococci, Diplococcus pneumoniae, non-penicillinase producing staphylococci and Streptococcus faecalis. These organisms are susceptible to amoxicillin at serum concentrations, which may be expected following the recommended doses. However, some of the organisms were susceptible to amoxicillin only at concentrations achieved in the urine (see INDICATIONS). Escherichia coli isolates are becoming increasingly resistant to amoxicillin in vitro due to the presence of penicillinase-producing strains. Strains of gonococci which are relatively resistant to benzylpenicillin may be sensitive to amoxicillin. The following in vitro data are available, but their clinical significance is unknown. In vitro data for amoxicillin vs. clinical pathogens Organism (n) MIC90 (mcg/ml) S. pneumoniae (3493) 1 2 H. influenzae (3366) 1 32 S. pyogenes (683) H. influenzae b-lac + (725) 1 32 H. influenzae b-lac (2587) 1 1 Klebsiella pneumonia (1161) 1 32 M. catarrhalis (864) 1 16 MSSA (1232) 1 32 Bacteroides fragilis group (80) 2 64 Fusobacterium sp (23) 2 8 Clostridium difficile (21) 2 2 N. gonorrhoeae (34) Data from the Augmentin Global Surveillance Study: June December 2000 from USA, Canada, Brazil, Mexico, Hong Kong, Australia, France, Belgium, Italy, Netherlands, Spain, Sweden and the UK. 2 Data from , France (Dubreuil L et al, In vitro evaluation of nitazoxanide and tizoxanide against anaerobes and aerobic organisms. Antimicrob Agents Chemother. 40(10), ) 3 Data from , UK (Wise R et al, In vitro activity of the tricyclic β-lactam GV Antimicrob Agents Chemother. 40(5), ) A positive β-lactamase test predicts resistance to penicillin, ampicillin and amoxicillin. The following are rates of resistance to amoxicillin for common pathogens in Australia. Rates of resistance to amoxicillin for common pathogens in Australia Organism Average Resistance (%) B. fragilis 100 Enterobacter spp. 96 Klebsiella spp. 98 M. catarrhalis 94 P. aeruginosa 100 S. aureus (methicillin-susceptible) 85 Enterococcus faecalis 0.2 Enterococcus faecium 80 E. coli 45.4 H. influenzae 20.3 P. mirabilis 14 S. pneumoniae 0.6 (fully resistant) 3.2(intermediate resistance)

3 ALPHAMOX PRODUCT INFORMATION 3 Breakpoints Streptococcus pneumoniae: S -2 mcg/ml; I = 4 mcg/ml; R 8 mcg/ml Note: Because amoxicillin has greater in vitro activity against S. pneumoniae than does ampicillin, the majority of S. pneumoniae strains with intermediate susceptibility to ampicillin are fully susceptible to amoxicillin. Susceptibility Tests Dilution or Diffusion Techniques Either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. NCCLS). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. A report of Susceptible indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of Intermediate indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to the alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of the drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected. Note: The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections. This information gives only an approximate guidance on probabilities whether organisms will be susceptible to amoxicillin. Susceptibility to amoxicillin will vary with geography and time and local susceptibility data should be consulted where available and microbiological sampling and susceptibility testing performed where necessary. Cross-Resistance Other β-lactams, β-lactam/β-lactamase inhibitor combinations and cephalosporins. Resistance Mechanisms Production of penicillinase, altered penicillin binding proteins. Pharmacokinetics Absorption Amoxicillin is stable in the presence of gastric acid and is rapidly and well absorbed after oral administration, even in the presence of food. Distribution Amoxicillin diffuses rapidly into most body tissues and fluids, with the exception of brain and spinal fluid except when meninges are inflamed. Amoxicillin has been shown to diffuse into sputum and saliva and is excreted mainly via the urine where it exists in a high concentration. The amount to be found in the bile is variable depending on normal biliary secretory function.

4 ALPHAMOX PRODUCT INFORMATION 4 Excretion The half-life of amoxicillin is 61.3 minutes with normal renal function, and in the absence of renal function 16 to 20 hours. Amoxicillin is excreted in the urine both unchanged and as penicilloic acid. About 75% of a 1 g dose is excreted in the urine in 6 hours in the presence of normal renal function (60% as amoxicillin and 15% as penicilloic acid). However, only 32% of a 3 g dose is excreted via the urine as the biologically active component in 8 hours (by which time most of the urinary excretion is complete). This proportional difference in the amount excreted from the different doses reflects a lack of linearity between doses and extent of absorption with a levelling off at higher doses of oral amoxicillin. Excretion of amoxicillin can be delayed by concurrent administration of probenecid, thus prolonging its therapeutic effect. Amoxicillin is not highly protein-bound, being only 17% protein-bound in serum as measured by ultrafiltration or equilibrium dialysis. The average peak serum levels resulting from the oral administration of 250 mg and 500 mg amoxicillin are 5 mcg/ml and 6.6 to 10.8 mcg/ml respectively, occurring one to two hours after administration. Measurable serum levels of amoxicillin are present eight hours after ingestion of a single oral dose. INDICATIONS Treatment of the following infections due to susceptible strains of sensitive organisms. Note: therapy should be guided by bacteriological studies, including sensitivity tests, and by clinical response. However, in emergency cases where the causative organism has not been identified, therapy with amoxicillin may be useful. Clinical judgement will decide whether combination with another antibiotic would provide a sufficiently broad spectrum of activity pending sensitivity test results. Skin and Skin Structure Staphylococcus, non-penicillinase producing; Streptococcus; E. coli (See Microbiology). Respiratory (Acute and Chronic) H. influenzae; Streptococcus; S. pneumoniae; staphylococcus, non-penicillinase producing; E. coli (see Microbiology). Genitourinary Tract (complicated and uncomplicated, Acute and Chronic) P. mirabilis; S. faecalis; E. coli (see Microbiology). Gonorrhoea N. gonorrhoeae (non-penicillinase producing). Prophylaxis of Endocarditis Amoxiillin may be used for the prophylaxis of bacterial endocarditis in individuals at particular risk, such as those with a prosthetic heart valve or those who have previously had endocarditis. CONTRAINDICATIONS Amoxicillin is a penicillin and should not be given to patients with a history of hypersensitivity to beta-lactam antibiotics (e.g. penicillins, cephalosporins).

5 ALPHAMOX PRODUCT INFORMATION 5 PRECAUTIONS Hypersensitivity (anaphylactic) Reactions Serious, and occasionally fatal, hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy. Before commencing therapy with any penicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, appropriate therapy should be instituted and ALPHAMOX therapy discontinued. Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation, should also be administered as indicated. Clostridium difficile Associated Diarrhoea Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including amoxicillin. A toxin produced with Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used. Oral Anticoagulants Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. Potential for Microbial Overgrowth or Bacterial Resistance As with any potent drug, periodic assessment of renal, hepatic and haematopoietic function should be made during prolonged therapy. The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), the drug should be discontinued and/or appropriate therapy instituted. Use in Patients with Mononucleosis Amoxicillin, an aminopenicillin, is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis, in the presence of which there is a high incidence of rash if amoxicillin is used. Patients with Lymphatic Leukaemia Amoxicillin should be given with caution to patients with lymphatic leukaemia, since they are especially susceptible to ampicillin-induced skin rashes. Patients with Acute Lower Urinary Tract Infection Following single dose therapy of acute lower urinary tract infections, the urine should be cultured. A positive culture may be evidence of a complicated or upper urinary tract infection and call for a longer or larger course of therapy. Adequate fluid intake and urinary output must be maintained in patients receiving high doses of amoxicillin.

6 ALPHAMOX PRODUCT INFORMATION 6 Patients with Renal Impairment Dosage should be adjusted in patients with renal impairment (see DOSAGE AND ADMINISTRATION). Use in Pregnancy (Category A) Animal studies with amoxicillin have shown no teratogenic effects. Amoxicillin has been in extensive clinical use since 1972 and its suitability in human pregnancy has been well documented in clinical studies. Amoxicillin may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment. Australian categorisation definition of Category A. Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Labour and Delivery Oral ampicillin class antibiotics are generally poorly absorbed during labour. Studies in guinea pigs have shown that intravenous administration of ampicillin decreased the uterine tone, frequency of contractions, height of contractions and duration of contractions. However, it is not known whether the use of amoxicillin in humans during labour or delivery has immediate or delayed adverse effects on the foetus, prolongs the duration of labour or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary. Use in Lactation Ampicillin class antibiotics are excreted in the milk; therefore, caution should be exercised when amoxicillin is administered to breastfeeding women. Effects on Laboratory Tests Oral administration of amoxicillin will result in high urine concentrations of amoxicillin. Since high urine concentrations of amoxicillin may result in false positive reactions when testing for the presence of glucose in urine using Clinitest, Benedict's Solution or Fehling's Solution, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix or Testape) be used. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone and oestradiol has been noted. This effect may also occur with amoxicillin. INTERACTIONS WITH OTHER MEDICINES Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use with ALPHAMOX may result in increased and prolonged blood levels of amoxicillin. The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. Similar reactions can be expected with amoxicillin. In common with other broad-spectrum antibiotics, amoxicillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. In the literature, there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin.

7 ALPHAMOX PRODUCT INFORMATION 7 Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin. ADVERSE EFFECTS As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins. The following adverse reactions have been reported as associated with the use of amoxicillin: Infections and infestations Mucocutaneous candidiasis have been reported very rarely. Gastrointestinal Nausea, vomiting, diarrhoea, intestinal candidiasis and antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) have been reported rarely. Black hairy tongue has been reported very rarely (see PRECAUTIONS). Hypersensitivity Reactions Erythematous maculopapular rashes, urticaria and pruritus have been reported occasionally. Rarely, skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and bullous, exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. As with other antibiotics, severe allergic reactions including angioneurotic oedema, anaphylaxis, serum sickness, hypersensitivity vasculitis and interstitial nephritis have been reported rarely. Whenever such reactions occur, ALPHAMOX should be discontinued. (Note: urticaria, other skin rashes and serum sickness-like reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids). Anaphylaxis is the most serious reaction experienced (see PRECAUTIONS). Hepatic A moderate rise in AST and/or ALT has occasionally been noted, but the significance of this finding is unknown. As with other beta-lactam antibiotics, hepatitis and cholestatic jaundice have been reported rarely. Haemic and Lymphatic Systems Reactions such as anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia and leucopenia (including severe neutropenia or agranulocytosis) have been reported during therapy with other penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Prolongation of bleeding time and prothrombin time have also been rarely reported. Renal and Urinary Tract Disorders Interstitial nephritis, crystalluria (see OVERDOSAGE). Central Nervous System Effects CNS effects have been seen rarely. They include hyperkinesia, dizziness and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses. Miscellaneous Superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.

8 ALPHAMOX PRODUCT INFORMATION 8 DOSAGE AND ADMINISTRATION The following recommended doses are for patients with normal renal function. Upper Respiratory Tract Infections, Genitourinary Tract Infections, Skin and Soft Tissue Infections Adults. 250 mg every 8 hours. Children (under 20 kg). 20 mg/kg/day in equally divided doses every 8 hours. In severe infections or those caused by less susceptible organisms, 500 mg every 8 hours for adults and 40 mg/kg/day in equally divided doses every 8 hours for children may be needed. Lower Respiratory Tract Infections Adults. 500 mg every 8 hours. Children (under 20 kg). 40 mg/kg/day in equally divided doses every 8 hours. Urethritis, Gonococcal Adults. 3 grams as a single dose. Cases of gonorrhoea with a suspected lesion of syphilis should have darkfield examinations before receiving ALPHAMOX and monthly serological tests for a minimum of four months. Acute, Uncomplicated Lower Urinary Tract Infections in non-pregnant adult females Adults. 3 grams as a single dose. Note: Experience in neonates is too limited to make any recommendations regarding dosage or the appropriateness of the oral route. The children's dosage is intended for individuals whose weight will not cause dosage to be calculated greater than that recommended for adults. Children weighing more than 20 kg should be dosed according to the adult recommendations. Renal Impairment In renal impairment, the excretion of the antibiotic will be delayed, and depending on the degree of impairment, it may be necessary to reduce the total daily dosage. In patients receiving peritoneal dialysis, the maximum recommended dose is 500 mg/day. Amoxicillin may be removed from the circulation by haemodialysis. It should be recognised that in the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisals are necessary. Smaller doses than those recommended above should not be used. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy. Treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days treatment for any infection caused by haemolytic streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis. Prophylaxis of Endocarditis Prophylaxis of Endocarditis Based on the recommendations of the British Society for Antimicrobial Chemotherapy

9 ALPHAMOX PRODUCT INFORMATION 9 Condition Dental Procedures. Prophylaxis for patients undergoing extraction, scaling or surgery involving gingival tissues and who have not received a penicillin in the previous month. (N.B. Patients with prosthetic heart valves should be referred to hospital- see below). Patient not having general anaesthetic. Patient having general anaesthetic: oral antibiotics not appropriate. Dental Procedures. Patients for whom referral to hospital is recommended: (a) patients to be given a general anaesthetic who have been given a penicillin in the previous month. (b) patients to be given a general anaesthetic who have a prosthetic heart valve. (c) patients who have had one or more attacks of endocarditis. Genito-urinary Surgery or Instrumentation. Prophylaxis for patients who have no urinary tract infection and who are to have genito-urinary surgery or instrumentation under general anaesthesia. Obstetric and Gynaecological Procedures and Gastro-intestinal Procedures. Routine prophylaxis is recommended only for patients with prosthetic heart valves. Surgery or Instrumentation of the Upper Respiratory Tract Patients other than those with prosthetic heart valves. Patients with prosthetic heart valves. Adults' Dosage (including elderly) Amoxicillin 3 grams orally, 1 hour before procedure. A second dose may be given 6 hours later, if considered necessary. Amoxicillin 1 gram IM immediately before induction; with 500 mg orally, 6 hours later. Initially: Amoxicillin 1 gram IM with 120mg gentamicin IM, immediately prior to anaesthesia (if given) or 15 minutes prior to dental procedure. Followed by (6 hours later): amoxicillin 500 mg orally. Initially: Amoxicillin 1 gram IM with 120mg gentamicin IM, immediately before induction. Followed by (6 hours later): Amoxicillin 500 mg orally or IM according to clinical condition. Amoxicillin 1 gram IM immediately before induction. Followed by (6 hours later): Amoxicillin 500 mg IM. Initially: Amoxicillin 1 gram IM with 120mg gentamicin IM, immediately before induction. Followed by (6 hours later): Amoxicillin 500 mg IM. Children's Dosage Half adult dose. Under 5 years: Quarter adult dose. Half adult dose. The doses of amoxicillin should be half the adult dose. The dose of gentamicin should be 2mg/kg. The doses of Amoxicillin should be half the adult dose. The dose of gentamicin should be 2mg/kg. Half adult dose. The dose of amoxicillin should be half the adult dose. The gentamicin dose should be 2mg/kg. Notes Note 1. Prophylaxis with alternative antibiotics should be considered if the patient has received a penicillin within the previous month, or is allergic to penicillin. Note 2: To minimise pain on injection, amoxicillin should be dissolved in sterile lignocaine 1% solution. (see Administration) See Note 2. Note 3. Amoxicillin and gentamicin should not be mixed in the same syringe. Note 4. Please consult the appropriate data sheet for full prescribing information on gentamicin See Notes 2, 3 and 4 above. See Note 2 above. Note 5. The second dose of amoxicillin may be administered orally as syrup. See Notes 2, 3, 4 and 5 above.

10 ALPHAMOX PRODUCT INFORMATION 10 OVERDOSAGE Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water/ electrolyte imbalance should be treated symptomatically. During the administration of high doses of amoxicillin, adequate fluid intake and urinary output must be maintained to minimise the possibility of amoxicillin crystalluria. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see PRECAUTIONS). Amoxicillin can be removed from the circulation by haemodialysis. For further advice on the management of overdose or suspected overdose, contact the Poisons Information Centre on PRESENTATION AND STORAGE CONDITIONS ALPHAMOX 250 Amoxicillin 250 mg capsule: cream body, green cap; Blister pack 20, 30s; Bottle 4, 20, 500s. Store below 25 C. ALPHAMOX 500 Amoxicillin 500 mg capsule: cream body, green cap; Blister pack 20, 30, 28, 6s; Bottle 4, 20, 500s. Store below 25 C. ALPHAMOX 125 Amoxicillin 125 mg/5ml powder for oral suspension: white to cream coloured, raspberry flavoured, sugar free; 100mL when reconstituted. Store below 25 C. After reconstitution, sugar free suspension should be stored at 2 to 8 C and used within 14 days. Discard remaining portion thereafter. ALPHAMOX 250 Amoxicillin 250 mg/5ml powder for oral suspension: white to cream coloured, raspberry flavoured, sugar free; 100mL when reconstituted. Store below 25 C. After reconstitution, sugar free suspension should be stored at 2 to 8 C and used within 14 days. Discard remaining portion thereafter. * Not all presentations are marketed in Australia. Reconstitution For 125 mg/5ml suspension, add 90 ml of water in small quantities. For 250 mg/5ml suspension, add 80 ml of water in small quantities. Shake vigorously. Shake well before use. Refrigerate prepared mixture. Do not freeze. POISON SCHEDULE OF THE MEDICINE S4 Prescription Only Medicine

11 ALPHAMOX PRODUCT INFORMATION 11 NAME AND ADDRESS OF THE SPONSOR Alphapharm Pty Limited (ABN ) Level 1, 30 The Bond 30 Hickson Road Millers Point NSW DATE OF FIRST INCLUSION ON THE AUSTRALIAN REGISTER OF THERAPEUTIC GOODS (THE ARTG) ALPHAMOX 125mg/5mL and 250mg/5mL 6/12/1995 ALPHAMOX 250 mg and 500 mg capsules 20/09/1991 DATE OF MOST RECENT AMENDMENT 21/11/2017 alphamox_pi\nov17/01